COMMENTARY

The risk of suicide in schizophrenia is similar to that in mood disorders, and is much higher than in the general population. The risk of suicidal behaviour is therefore an important problem, complicating clinical care in schizophrenia. Meltzer et al describe a pivotal study of treating suicidal behaviour in schizophrenia and schizoaffective disorder. This is the first randomised controlled trial to suggest the superiority of clozapine over another atypical antipsychotic (olanzapine) for this indication. The study supports a number of previous uncontrolled observations.

Selecting olanzapine as the comparator treatment was somewhat ambitious given that this drug has some antidepressant effects. Furthermore, several studies have found that olanzapine and clozapine have comparable antipsychotic efficacy. The finding that clozapine is superior to olanzapine in this context is therefore even more remarkable.

Doses were based on clinical judgment. While the mean olanzapine dose was close to that used in the United States for schizophrenia, the clozapine dose was relatively low. The authors hypothesise that the low clozapine dose was because most patients were not treatment refractory. The mechanism of effectiveness of this low dose may be separate from that implicated in the general antipsychotic activity of clozapine (which typically requires higher doses).

It is important to note that antidepressants were prescribed concomitantly with olanzapine (55.1%) and clozapine (49.1%). The difference in concomitant antidepressant prescriptions was statistically significant. From a clinical standpoint, it is perhaps more important to realise that neither of the two antipsychotics alone had sufficient antidepressant or anti-suicidal effect. Instead, about half of the participants required antidepressant supplementation. Clinicians may be interested in an analysis investigating the effect of diagnosis (schizophrenia versus schizoaffective disorder) on this concomitant antidepressant use.

Overall, this is a landmark study that will influence clinical practice for years to come. The risk of suicide is a major cause of hospitalisation for people with schizophrenia or schizoaffective disorder. The other major cause of hospitalisation is risk of violence. Aggression against self (suicidal behaviour) and aggression against others have a number of common underlying neurobiological mechanisms. Clozapine is a relatively specific treatment for both conditions. An analysis of any measure of aggression or hostility in Meltzer’s database would be interesting.